Platinum compounds that inhibit constitutive STAT3 signaling and induce cell cycle arrest and apoptosis of malignant cells

Abstract

The subject invention concerns a compound and compositions having activity as an inhibitor of Stat3 protein and methods of using the compound and compositions. In one embodiment, a compound of the invention has the structure shown in formula I, formula II, or formula III. The subject invention also concerns methods of using the compounds and compositions of the invention.

We claim: 
     
       1. A method for treating a subject having an oncological disorder associated with aberrant or excessive Stat3 activity or interaction in a cell, comprising administering an effective amount of a compound having the structure shown in formula I, formula II, or formula III: 
       
         
           
           
               
               
           
         
       
       to the subject, wherein x is a monovalent anion, and wherein the oncological disorder is breast cancer, lung cancer, prostate cancer, multiple myeloma, melanoma, lymphoma, head and neck squamous cell carcinoma, or pancreatic cancer. 
     
     
       2. The method of  claim 1 , wherein the method further comprises, prior to said administering, determining that the oncological disorder is associated with aberrant or excessive Stat3 activity or interaction in a cell. 
     
     
       3. The method of  claim 2 , wherein said determining comprises measuring a level of Stat3 activity or interaction in a biological sample collected from the subject and comparing the measured level to a reference level of Stat3 activity or interaction. 
     
     
       4. The method of  claim 1 , wherein the subject is a non-human mammal. 
     
     
       5. The method of  claim 1 , wherein the subject is human. 
     
     
       6. A method for inducing apoptosis in a malignant cell aberrantly or constitutively expressing active Stat3, comprising contacting the cell with an effective amount of a compound having the structure shown in formula I, formula II, or formula III: 
       
         
           
           
               
               
           
         
       
       wherein x is a monovalent anion, and wherein the cell is a breast cancer cell, lung cancer cell, prostate cancer cell, multiple myeloma cell, lymphoma cell, melanoma cell, head and neck squamous carcinoma cell, or pancreatic cancer cell. 
     
     
       7. The method of  claim 6 , wherein the method further comprises, prior to said contacting, determining that the cell or a representative cell aberrantly or constitutively expresses active Stat3. 
     
     
       8. The method of  claim 7 , wherein said determining comprises measuring a level of Stat3 activity or interaction in the cell or representative cell and comparing the measured level to a reference level of Stat3 activity or interaction. 
     
     
       9. The method of  claim 6 , wherein said contacting comprises contacting the cell with a composition comprising the compound and a carrier, buffer, adjuvant, or a combination of two or more of the foregoing. 
     
     
       10. The method of  claim 6 , wherein said contacting is carried out in vitro. 
     
     
       11. The method of  claim 6 , wherein said contacting is carried out in vivo. 
     
     
       12. The method of  claim 11 , wherein said contacting comprises administering the effective amount of the compound to a human. 
     
     
       13. The method of  claim 1 , wherein the compound has the structure shown in formula (I). 
     
     
       14. The method of  claim 1 , wherein the compound has the structure shown in formula (II). 
     
     
       15. The method of  claim 1 , wherein the compound has the structure shown in formula (III). 
     
     
       16. The method of  claim 6 , wherein the compound has the structure shown in formula (I). 
     
     
       17. The method of  claim 6 , wherein the compound has the structure shown in formula (II). 
     
     
       18. The method of  claim 6 , wherein the compound has the structure shown in formula (III).